薄层色谱法拆分几种β-受体阻滞剂药物的研究
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摘要
许多药物或生理上非常重要的化合物都是手性的，这些化合物的光学异构体在药理上有较大的差异，在某些情况下，其光学异构体也许会产生难以预料的副作用。因此，为提高药物活性，降低副作用以及指导药物生产和质量控制，提供光学纯化合物已成为生物化学和药物学的一个重大课题。1992年FDA发布了手性药物指导原则，要求所有在美国上市的消旋体新药，均需提供详细报告，说明药物中所含对映体各自的药理作用、毒性和临床效果。因此，外消旋手性药物的拆分非常重要。
本文详细分析了手性拆分技术的发展趋势，综述了现有的手性拆分方法，分析了各种方法的利弊。深入研究了D-10-樟脑磺酸铵作为薄层色谱流动相手性离子对添加剂拆分盐酸普萘洛尔对映体，通过单因素实验考察了展开体系、温度、预饱和时间、pH、手性离子对试剂浓度以及湿度等的影响，得到了拆分的最佳色谱条件；采用β-环糊精固载薄层色谱法拆分了盐酸普萘洛尔，并对拆分的流动相组成、配比和手性选择体固载量进行了考察，优化了分离条件，得到了拆分的最佳条件，并初步探讨了β-环糊精固载薄层色谱法拆分盐酸普萘洛尔的机理。
同时研究了D-10-樟脑磺酸铵作为薄层色谱流动相手性离子对添加剂拆分酒石酸美托洛尔和阿替洛尔对映体，讨论了展开体系、温度、预饱和时间、pH、手性离子对试剂浓度以及湿度对拆分的影响，分别得到了酒石酸美托洛尔和阿替洛尔的最佳分离条件；也深入讨论了β-环糊精固载薄层色谱法拆分酒石酸美托洛尔和阿替洛尔对映体的条件如：展开体系，温度和手性选择体固载量等。
Many drugs or necessary-physiological compounds are chiral, and the optical isomers of these compounds are very different in physiology, in some cases, perhaps the optical isomers have unexpected side-effects.So, in order to improve drug activity, decrease side-effect and process drug manufacturing and quality controlling, supplying optically pure compounds has become an important subject in biochemistry and pharmacology. Guidelines of chiral drugs, which was published by FDA in 1992, demanded that detailed reports of racemic new drugs should be provided before entering the market in USA, which should prove physiology effects, toxicity and clinical results of isomers in drugs.In a word, the enantioseparation of racemic drugs is very important.
The trend of development of chiral techniques was analyzed, and the forthcoming chiral separation methods and their advantages and disadvantages were reviewed detailedly in this paper.The enantioseparation of propranolol by TLC using D-10-camphor ammonium sulfonate as chiral ion-pair agent in the mobile phase was studied in depth. The effects of the mobile phase, temperature, pre-saturation time, pH, the concentration of ion-pair agent and humidity on separation were investigated by single-factor experiments, and the optimal chroatographic conditions were concluded; Secondly, resolution of propranolol hydrochloride enantiomers usingβ-cyclodextrin impregnated thin-layer chromatography was studied synchronously, the makeup of the mobile phase and quantity of the impregnated chiral selectors were studied, the conditions of separation were optimized, then concluded the optimal conditions of separation.
In the meantime, we studied the enantioseparation of metoprolol and atenolol by TLC using D-10-camphor ammonium sulfonate as chiral ion-pair agent in the mobile phase , discussed the effects of the mobile phase, temperature, pre-saturation time, pH, the concentration of ion-pair agent and humidity on separation, and concluded respectively the optimal separation conditions of metoprolol and atenolol ;we also discussed the conditions of resolution of metoprolol and atenolol enantiomers usingβ-cyclodextrin impregnated thin-layer chromatography , such as the makeup of the mobile phase , temperature and quantity of the impregnated chiral selectors .etc.
本文详细分析了手性拆分技术的发展趋势，综述了现有的手性拆分方法，分析了各种方法的利弊。深入研究了D-10-樟脑磺酸铵作为薄层色谱流动相手性离子对添加剂拆分盐酸普萘洛尔对映体，通过单因素实验考察了展开体系、温度、预饱和时间、pH、手性离子对试剂浓度以及湿度等的影响，得到了拆分的最佳色谱条件；采用β-环糊精固载薄层色谱法拆分了盐酸普萘洛尔，并对拆分的流动相组成、配比和手性选择体固载量进行了考察，优化了分离条件，得到了拆分的最佳条件，并初步探讨了β-环糊精固载薄层色谱法拆分盐酸普萘洛尔的机理。
同时研究了D-10-樟脑磺酸铵作为薄层色谱流动相手性离子对添加剂拆分酒石酸美托洛尔和阿替洛尔对映体，讨论了展开体系、温度、预饱和时间、pH、手性离子对试剂浓度以及湿度对拆分的影响，分别得到了酒石酸美托洛尔和阿替洛尔的最佳分离条件；也深入讨论了β-环糊精固载薄层色谱法拆分酒石酸美托洛尔和阿替洛尔对映体的条件如：展开体系，温度和手性选择体固载量等。
Many drugs or necessary-physiological compounds are chiral, and the optical isomers of these compounds are very different in physiology, in some cases, perhaps the optical isomers have unexpected side-effects.So, in order to improve drug activity, decrease side-effect and process drug manufacturing and quality controlling, supplying optically pure compounds has become an important subject in biochemistry and pharmacology. Guidelines of chiral drugs, which was published by FDA in 1992, demanded that detailed reports of racemic new drugs should be provided before entering the market in USA, which should prove physiology effects, toxicity and clinical results of isomers in drugs.In a word, the enantioseparation of racemic drugs is very important.
The trend of development of chiral techniques was analyzed, and the forthcoming chiral separation methods and their advantages and disadvantages were reviewed detailedly in this paper.The enantioseparation of propranolol by TLC using D-10-camphor ammonium sulfonate as chiral ion-pair agent in the mobile phase was studied in depth. The effects of the mobile phase, temperature, pre-saturation time, pH, the concentration of ion-pair agent and humidity on separation were investigated by single-factor experiments, and the optimal chroatographic conditions were concluded; Secondly, resolution of propranolol hydrochloride enantiomers usingβ-cyclodextrin impregnated thin-layer chromatography was studied synchronously, the makeup of the mobile phase and quantity of the impregnated chiral selectors were studied, the conditions of separation were optimized, then concluded the optimal conditions of separation.
In the meantime, we studied the enantioseparation of metoprolol and atenolol by TLC using D-10-camphor ammonium sulfonate as chiral ion-pair agent in the mobile phase , discussed the effects of the mobile phase, temperature, pre-saturation time, pH, the concentration of ion-pair agent and humidity on separation, and concluded respectively the optimal separation conditions of metoprolol and atenolol ;we also discussed the conditions of resolution of metoprolol and atenolol enantiomers usingβ-cyclodextrin impregnated thin-layer chromatography , such as the makeup of the mobile phase , temperature and quantity of the impregnated chiral selectors .etc.
引文
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